Despite the growing use of fertility-enhancing therapies, little is known about the health of women with infertility, or the particular effects of ART treatments. Although some studies suggest health risks associated with ART, others point to the underlying infertility diagnosis as a greater risk factor. Research is needed to identify risks associated with ART, beyond underlying subfertility, distinguishing potential direct effects of ART (e.g. greater risk of cancer) from indirect effects of ART (e.g., facilitating pregnancies among older mothers or those involving complications such as multiple births). This proposal describes an innovative collaboration between Boston University School of Public Health, the Massachusetts Department of Public Health, the Society for Assisted Reproductive Technology, and the Centers for Disease Control and Prevention. The collaboration facilitates the creation of a unique longitudinally linked, population-based database that combines detailed clinical information on ART treatment and infertility diagnoses with the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System, which contains linked data on pregnancy, births, deaths, hospital utilization and costs, and as part of this project, will add data from the Massachusetts Cancer Registry. The resulting database will track health outcomes for women up to 8 years after treatment across four groups: women with pregnancies assisted by ART (~25,000), women without ART but subfertility indicators (~6,000), women with ART and no pregnancy beyond 20 weeks (~22,000) and women who give birth without ART or subfertility indicators (~305,000). This project addresses key limitations of prior ART research: limited subfertility comparison groups and a lack of population-based data and longitudinal measures of health for women. Two broad hypotheses will initially be tested: (1) Women whose pregnancies were conceived through ART have a higher risk of compromised health outcomes compared to: (a) women with indicators of subfertility but no ART and pregnancies of 20 weeks;and (b) women without indicators of subfertility or ART and pregnancies of 20 weeks;and (2) Women whose pregnancies were conceived through ART differ in their risks for compromised health by ART treatment parameters, infertility diagnoses and their interactions. Two additional analyses will examine health outcomes among important subgroups of women: (a) those with ART and no resulting pregnancy and (b) those with more than one pregnancy in the time frame studied, one of which involved ART and one which did not. The result will be the largest, most refined study ever undertaken on the short, immediate and long term effects of infertility and ART on the health of women. PUBLIC HEALTH RELEVANCE: Research has shown that women treated with assisted reproductive technology (ART) are at greater risk for adverse health outcomes, but prior studies have not determined how much of this increased health risk is related to ART treatment, the underlying infertility diagnosis, or their combination. The proposed project will link SART CORS clinical data from 2004 through 2012 to the Massachusetts Pregnancy to Early Life Longitudinal birth, fetal death and hospitalization data files as well as the Massachusetts Cancer Registry to develop the largest (more than 45,000 women with ART;6,000 women with subfertility indicators and no ART;and 305,000 women with a pregnancy and no ART) and most comprehensive US study to date examining the short, intermediate and long term (up to 8 years) impact of infertility and ART on the health of women. The study will examine health outcomes among women with subfertility indicators who undergo ART compared to those without ART or no subfertility indicators;among women with different ART treatments and infertility diagnoses;and among women who receive ART but do not conceive or have a pregnancy lasting less than 20 weeks.